The proposed investigations are to ascertain: i) the mechanisms responsible for the maintenance of plasmids in bacterial populations; ii) the nature and consequences of coevolution in bacteriophage and their hosts; iii) the ecological conditions and selection pressures responsible for the evolution and maintenance of restriction-modification systems; and iv) the ecological conditions and selection pressures responsible for the evolution and maintenance of temperate (as opposed to virulent) modes of bacteriophage replication. This investigation is to be performed at both a theoretical and empirical level. The former will involve the development and analysis of mathematical and computer simulation models of the population biology of bacteria with plasmids, virulent and temperate phage. The empirical portions of this investigation will be with naturally occuring, as well as laboratory strains of E. coli and its antibiotic resistance, R-plasmids, and virulent and temperate phage. Using experimental cultures of these organisms, estimates of the parameters of the models will be obtained and used for the numerical analysis. The validity and/or plausability of hypotheses generated from the analysis of these models and other sources will be tested with experimental (chemostat and serial transfer) populations of E. coli and its plasmids and phage and by the study of E. coli and phage from natural populations. --While this research is motivated primarily by the academic significance of these problems, the results obtained are anticipated to be of use for clinical epidemiological and other applied considerations of population biology of bacterial plasmids and viruses, e.g., the design of programs for the control of plasmid-borne multiple antibiotic resistance, the use of phage or plasmid-profile typing for bacterial clone idenfitication, and the design of programs for the use of bacteria and phage for biological control.